蛭田 勇樹 (ヒルタ ユウキ)

Hiruta, Yuki

写真a

所属(所属キャンパス)

理工学部 応用化学科 (矢上)

職名

准教授

経歴 【 表示 / 非表示

  • 2010年04月
    -
    2011年03月

    慶應義塾大学大学院, 理工学研究科, 助教(有期・研究奨励)

  • 2011年04月
    -
    2013年03月

    日本学術振興会, 特別研究員(DC2)

  • 2013年04月
    -
    2017年03月

    慶應義塾大学, 薬学部, 助教

  • 2017年04月
    -
    2023年03月

    慶應義塾大学, 理工学部, 専任講師

  • 2023年04月
    -
    継続中

    慶應義塾大学, 理工学部, 准教授

全件表示 >>

学歴 【 表示 / 非表示

  • 2004年04月
    -
    2008年03月

    慶應義塾大学, 理工学部, 応用化学科

    大学, 卒業

  • 2008年04月
    -
    2010年03月

    慶應義塾大学, 理工学研究科, 総合デザイン工学専攻

    大学院, 修了, 修士

  • 2010年04月
    -
    2013年03月

    慶應義塾大学, 理工学研究科, 総合デザイン工学専攻

    大学院, 修了, 博士

学位 【 表示 / 非表示

  • 博士(工学), 慶應義塾大学理工学研究科総合デザイン工学専攻, 論文

 

著書 【 表示 / 非表示

  • Development of Near-Infrared Fluorescent Mg<sup>2+</sup> Probe and Application to Multicolor Imaging of Intracellular Signals

    Shindo Y., Ikeda Y., Hiruta Y., Citterio D., Oka K., Methods in Molecular Biology, 2021年

     概要を見る

    Recent extensive studies revealed that the intracellular concentration of magnesium ions (Mg2+) is one of the important factors to regulate cellular functions. To evaluate the impact of Mg2+ concentration changes on intracellular signals or events, simultaneous imaging of Mg2+ with those phenomena is a powerful technique. The present protocol describes the synthesis and evaluation of near-infrared (NIR) fluorescent Mg2+-selective probes, named KMG-500 series, and the application to simultaneous imaging of the corresponding intracellular signal transductions and molecular events. The present protocol for multicolor imaging using fluorescent probes in the NIR and visible ranges is highly useful to reveal how multiple molecular events are correlated each other in each single cell.

論文 【 表示 / 非表示

  • Current advances in separation chemistry for antibody purification and analysis

    Deol S., Matsuda Y., Hiruta Y.

    Analytical Sciences 41 ( 5 ) 653 - 666 2025年05月

    研究論文(学術雑誌), 共著, 最終著者, 責任著者, 査読有り,  ISSN  09106340

     概要を見る

    Monoclonal antibodies (mAbs) have become essential in modern therapeutics, offering high specificity and efficacy in treating diseases such as cancer, autoimmune disorders, and infectious diseases. With the increasing demand for mAbs, robust analytical and purification technologies are critical to ensuring their safety, efficacy, and consistency. This review highlights recent advances in the application of HPLC for both mAb analysis and purification. In the analytical domain, techniques such as size exclusion chromatography (SEC), hydrophobic interaction chromatography (HIC), ion exchange chromatography (IEX), and reversed-phase chromatography (RPLC) are explored for their role in evaluating mAb structural attributes and post-translational modifications (PTMs). These methods are indispensable for ensuring stability and functionality while meeting stringent regulatory requirements. In the context of purification, Protein A affinity chromatography remains the gold standard for initial capture of mAb; however, challenges such as high cost and harsh elution conditions have prompted the development of alternative purification technologies. IEX, HIC, multimodal, and membrane chromatography are also critical in achieving high-purity mAb products through multistep workflows, including intermediate purification and polishing stages. This review emphasizes the central role of HPLC in addressing the complex challenges of mAb manufacturing and characterization. By integrating established and emerging chromatographic techniques, it provides insights into the future directions of therapeutic antibody development.

  • Bioluminescence readout lateral flow immunoassay using nanobody targeting aflatoxin B1

    Takahashi, S; Hiruta, Y; Citterio, D

    ANALYST 150 ( 8 ) 1563 - 1570 2025年04月

    研究論文(学術雑誌), 共著, 査読有り,  ISSN  0003-2654

     概要を見る

    Multiple signal detection methods are known for lateral flow immunoassays (LFIAs), with colorimetric approaches dominating the field. However, their limited sensitivity is a remaining challenge. Fluorescence-based signaling is regarded as a more sensitive method, but it comes at the cost of partial sacrifice of the user-friendliness of LFIAs due to the requirement of an excitation light source. In this context, bioluminescence providing an inherently high signal to noise ratio without the need of excitation light could be an attractive alternative. But only a few studies have demonstrated the application of bioluminescence signaling in LFIAs. This work aimed at the development of a simple bioluminescence-based LFIA for the detection of aflatoxin B1 (AFB1), used as a model target in a competitive LFIA format. Signal transduction was achieved by nanobody-nanoluciferase (Nluc) fusion proteins. These small-sized recombinant heavy-chain-only antibodies derived from the camelidae family directly linked with the Nluc enzyme produce high intensity glow-type bioluminescence in combination with the furimazine substrate. LFIA devices consisting of a sample pad, nitrocellulose membrane and absorbent pad with AFB1-BSA conjugate deposited at the test line on the nitrocellulose membrane, achieved an LOD of 0.26 ng mL<sup>−1</sup> for aqueous AFB1 solutions pre-mixed with Nanobody-Nluc and bioluminescence emission observed on an imaging system. More user-friendly LFIA devices with integrated conjugate pad and pre-deposited Nanobody-Nluc provided clear AFB1 concentration-dependent bioluminescence signals with low background and enabled readout with a standard digital camera, resulting in an LOD of 1.12 ng mL<sup>−1</sup>. Finally, the LFIA strips have been applied in AFB1-spiked oat milk samples. The LOD of 4.09 ng mL<sup>−1</sup> achieved in the real sample matrix is well below the maximum allowable residual concentration of AFB1 in the U.S. (20 ng mL<sup>−1</sup>).

  • Origami Paper-Based Immunoassay Device with CRISPR/Cas12a Signal Amplification

    Suzuki, H; Tong, GD; Nath, P; Hiruta, Y; Citterio, D

    ACS SENSORS 10 ( 3 ) 1811 - 1821 2025年03月

    研究論文(学術雑誌), 共著, 査読有り,  ISSN  2379-3694

     概要を見る

    In clinical diagnosis, the determination of target proteins at low concentration levels is generally performed by immunoassays, such as the enzyme-linked immunosorbent assay (ELISA), which is a time-consuming process. To date, paper-based ELISA platforms enabling faster and less expensive analysis have been developed, but their important issue for clinical applications is the limited sensitivity compared to conventional ELISA. To address this challenge, this paper introduces a simple, rapid, and highly sensitive detection method for non-nucleic acid targets achieved by integrating the CRISPR/Cas12a system into paper-based ELISA. An origami-type paper-based device enabling simple assay operation has been designed, and the detection of targets on the paper substrates is based on observing the fluorescence signal induced by the CRISPR/Cas12a enzyme cleaving a probe single-stranded DNA (ssDNA) labeled with fluorophore and quencher (FQ reporter). To enhance sensitivity, antibodies labeled with a network of multiple DNA activating the CRISPR/Cas12a enzyme have been utilized as detection antibodies. As a result, the developed device successfully boosted the detection sensitivity for both human IgG and the hepatitis B virus surface antigen (HBsAg). In particular, the limit of detection (LOD) for HBsAg was estimated to be 12 pg/mL, representing over 10-fold higher sensitivity compared with commercially available HBsAg ELISA kits (LOD: 200 pg/mL). In addition, the fluorescence response toward porcine whole blood samples containing different HBsAg concentrations was also confirmed by capturing images with a smartphone, followed by quantitative data analysis. These results demonstrate the potential applicability of the proposed platform for clinical tests at the point of care.

  • The latest developments of near-infrared fluorescent probes from NIR-I to NIR-II for bioimaging

    Kuronuma, Y; Watanabe, R; Hiruta, Y

    ANALYTICAL SCIENCES 41 ( 6 ) 737 - 757 2025年02月

    研究論文(学術雑誌), 共著, 最終著者, 責任著者, 査読有り,  ISSN  0910-6340

     概要を見る

    Abstract: Near-infrared I (NIR-I: 650–950 nm) fluorescence imaging is a powerful tool for deep-tissue biological imaging, addressing the limitations of photon penetration depth in the visible-light region. Over the past decade, NIR imaging has extended to the near-infrared II (NIR-II: 1000–1700 nm) region, offering high-resolution and low background imaging by suppressing light scattering, and autofluorescence of tissues. Near-infrared fluorescent probes from NIR-I to NIR-II, with diverse functionalities, are increasingly utilized across biological fields to meet various detection needs and to explore physiological events in real time and spatial dimensions. This review discusses recent advancements in small-molecule NIR fluorescent dyes and probes, particularly those based on cyanine and rhodamine scaffolds, highlighting examples of their applications in bioimaging.

  • Ratiometric Imaging for Quantification of Elevated Ca<sup>2+</sup> in Neurons Using Synthetic Low-Affinity Fluorescent Probe

    Kuronuma Y., Shindo Y., Kumada R., Sakama A., Citterio D., Oka K., Hiruta Y.

    ACS Chemical Neuroscience 16 ( 4 ) 649 - 658 2025年02月

    研究論文(学術雑誌), 共著, 最終著者, 責任著者, 査読有り,  ISSN  1948-7193

     概要を見る

    The availability of various calcium ion (Ca2+) fluorescent probes has contributed to revealing physiological events related to intracellular Ca2+. However, conventional probes face challenges for quantitatively and selectively visualizing high Ca2+ concentrations in cells induced by any stimuli, including biomolecules or electrical signal that disrupt Ca2+ homeostasis. In this report, we designed and synthesized a low-affinity ratiometric Ca2+ probe, KLCA-Fura, utilizing o-aminophenol-N,N-diacetate-O-methylene-methylphosphinate (APDAP) as a ligand, for which we recently demonstrated the suitability as a new low-affinity ligand for Ca2+. KLCA-Fura showed a blue shift in excitation wavelength with increasing Ca2+ concentration based on the intramolecular charge transfer (ICT). Its affinity for Ca2+ is lower than commercially available conventional Ca2+ probes. Furthermore, the selectivity for Ca2+ and the fluorescence intensity were considered sufficient to accurately detect Ca2+. The corresponding acetoxymethyl ester, KLCA-FuraAM, was synthesized for intracellular imaging and applied to Ca2+ quantification in neurons. KLCA-FuraAM enabled quantitative ratiometric monitoring of the two-step Ca2+ concentration increase induced by glutamate stimulation. While this two-step response was not clearly observed with a commercially available low-affinity ratiometric Ca2+ probe, Fura-FF, KLCA-FuraAM has demonstrated the potential to quantitatively visualize the behavior of high Ca2+ concentrations. The ratiometric low-affinity Ca2+ probe, KLCA-Fura, is expected to be a powerful tool for discovering new functions of Ca2+ in neurons.

全件表示 >>

KOARA(リポジトリ)収録論文等 【 表示 / 非表示

全件表示 >>

研究発表 【 表示 / 非表示

  • 機能性高分子を用いた液体クロマトグラフィー充填剤の開発と医薬品分析への応用

    第35回クロマトグラフィー科学会議, 

    2024年11月

    口頭発表(招待・特別)

  • ペプチドミメティック分子設計によるpH応答性高分子の開発

    蛭田 勇樹

    第73回高分子討論会, 

    2024年09月

    口頭発表(一般)

  • スピロ環化平衡を利用したpH応答性近赤外蛍光シアニンプローブ

    蛭田 勇樹

    日本分析化学会第73年会, 

    2024年09月

    口頭発表(一般)

  • Cation/anion-exchange mode switching chromatography utilizing pH-responsive polymer for pharmaceutical separations

    Yuki Hiruta

    HPLC 2024, 

    2024年07月

    ポスター発表

  • Evaluation of hydrophilic brush copolymers on biodistribution for tumor-targeted carriers of diagnostic drugs

    Yuki Hiruta

    第40回日本DDS学会学術集会, 

    2024年07月

    口頭発表(一般)

全件表示 >>

競争的研究費の研究課題 【 表示 / 非表示

  • がんバイオマーカー応答性高分子を基盤とした光セラノスティクスプラットフォーム構築

    2023年04月
    -
    2026年03月

    文部科学省, 日本学術振興会 科学研究費助成事業 国際共同研究加速基金(国際共同研究強化(A)), 研究代表者

  • 生命科学研究を拓く生物発光技術の開発

    2023年04月
    -
    2024年03月

    文部科学省, 日本学術振興会 科学研究費助成事業 基盤研究(B), 補助金,  研究分担者

  • がんバイオマーカー応答性高分子設計を戦略とした光セラノスティクス薬剤の開発

    2021年04月
    -
    2024年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 蛭田 勇樹, 基盤研究(C), 補助金,  研究代表者

  • 時空間トランススケールイメージングを可能にする超分子ケージドルシフェリンの開発

    2021年04月
    -
    2023年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 蛭田 勇樹, 新学術領域研究(研究領域提案型), 補助金,  研究代表者

  • 時空間トランススケールイメージングを可能にする高分子ケージドルシフェリンの開発

    2019年04月
    -
    2021年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 蛭田 勇樹, 新学術領域研究(研究課題提案型), 補助金,  研究代表者

全件表示 >>

受賞 【 表示 / 非表示

  • クロマトグラフィー科学会奨励賞

    2024年11月, クロマトグラフィー科学会, 機能性高分子を用いた液体クロマトグラフィー充填剤の開発と医薬品分析への応用

    受賞区分: 国内学会・会議・シンポジウム等の賞

  • Best Poster Award HPLC 2022, San Diego

    2022年06月

    受賞区分: 国際学会・会議・シンポジウム等の賞

  • Outstanding Reviewer for journal of Materials Chemistry B

    2021年03月

    受賞区分: 出版社・新聞社・財団等の賞

  • 日本分析化学会奨励賞

    2020年08月, 公益社団法人日本分析化学会, 精密分子設計に基づくバイオイメージングプローブの開発と応用

    受賞区分: 国内学会・会議・シンポジウム等の賞

  • 高分子研究奨励賞

    Development of stimuli-responsive polymer materials for application to medical analysis, 2020年05月, 公益社団法人高分子学会, 医療分析への応用を志向した刺激応答性高分子材料の開発

    受賞区分: 国内学会・会議・シンポジウム等の賞

全件表示 >>

 

担当授業科目 【 表示 / 非表示

  • 応用化学輪講

    2025年度

  • 機器分析総論

    2025年度

  • ナノスケール科学ジョイントセミナー

    2025年度

  • マテリアルデザイン科学ジョイントセミナー

    2025年度

  • 自然科学実験

    2025年度

全件表示 >>

 

所属学協会 【 表示 / 非表示

  • クロマトグラフィー科学会会員, 

    2016年01月
    -
    継続中
  • 高分子学会会員, 

    2016年01月
    -
    継続中
  • 日本DDS学会会員, 

    2014年04月
    -
    継続中
  • 日本薬学会会員, 

    2014年01月
    -
    継続中
  • 日本化学会会員, 

    2010年01月
    -
    継続中

全件表示 >>

委員歴 【 表示 / 非表示

  • 2024年11月
    -
    継続中

    生物発光化学発光研究会世話人, 生物発光化学発光研究会

  • 2024年03月
    -
    継続中

    Associate Editor in Analytical Sciences, The Japan Society for Analytical Chemistry

  • 2021年01月
    -
    2022年12月

    関東支部常任幹事 , 日本分析化学会

  • 2019年12月
    -
    2021年11月

    化学グランプリ・オリンピック委員会 グランプリ小委員会 委員, 公益社団法人日本化学会

  • 2018年04月
    -
    継続中

    代議員, 日本分析化学会

全件表示 >>